A case of left atrial myxoma accompanied by pancytopenia and pathological findings

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Acta Medica Okayama

Volume28,Issue6 1974 Article6

D

^ECEMBER

1974

A case of left atrial myxoma accompanied by pancytopenia and pathological findings

suggestive of pulmonary hypertension

Koichi Kawanishi^∗ Keiichiro Sato^† Tadashi Ofuji^‡ Katsuo Ogawa^∗∗

∗Okayama University,

†Okayama University,

‡Okayama University,

∗∗Okayama University,

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suggestive of pulmonary hypertension ^∗

Koichi Kawanishi, Keiichiro Sato, Tadashi Ofuji, and Katsuo Ogawa

Abstract

A case of left atrial myxoma accompanied by peculiar symptoms is reported. A 15-year old boy had progressive congestive heart failure and three episodes of acute attacks of panctyopenia.

The anemia was accompanied by helmet-shaped, broken red blood cells, erythroid hyperplasia and elevation of indirect bilirubin. The thrombocytopenia gave rise to hemorrhagic tendency of the skin and mucous membrane. The leukocytopenia was seen at the same time. The patient also had general constitutional disturbances showing generalized malaise, persistent fever, elevation of erythrocyte sedimentation rate, positive C-reactive protein, pulmonary infection and anginal attacks. Postmortem examinations revealed a left atrial myxoma and intricated pulmonary changes.

There was obliterative endarteritis of the left coronary branch and pulmonary arteries. The interstitial pulmonary fibrosis was also prominent. The pancytopenia should have been induced by the mechanical damage of circulating blood cells by the left atrial myxoma. The pathological findings of the lungs were highly suggestive of pulmonary hypertension, which was assumed to be due to mitral block caused by the atrial myxoma.

∗PMID: 4282003 [PubMed - indexed for MEDLINE] Copyright cOKAYAMA UNIVERSITY MEDICAL SCHOOL

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Acta Med. Okayama 28, 433-440 (1974)

A CASE OF LEFT ATRIAL MYXOMA ACCOMPANIED BY PANCYTOPENIA AND PATHOLOGICAL

FINDINGS SUGGESTIVE OF PULMONARY HYPERTENSION

KoichiKAWANISHI*, KeiichiroSATO*,

TadashiOFUJI* and KatsuoOcAWA**

*Department of Internal Medicine (Director: Prof. T. Ofuji)

** DepartmentrifPathology, Okayama University Medical School, Okayama, Japan (Director: Prrif. K. Ogawa)

Received for publication, May 10, 1974

Abstract: A case of left atrial myxoma accompanied by peculiar symptoms is reported. A 15-year old boy had progressive congestive heart failure and three episodes of acute attacks of panctyopenia.

The anemia was accompanied by helmet-shaped, broken red blood cells, erythroid hyperplasia and elevation of indirect bilirubin. The thrombocytopenia gave rise to hemorrhagic tendency of the skin and mucous membrane. The leukocytopenia was seen at the same time.

The patient also had general constitutional disturbances showing generalized malaise, persistent fever, elevation of erythrocyte sedimentation rate, positive C-reactive protein, pulmonary infection and anginal attacks. Postmortem examinations revealed a left atrial myxoma and intricated pulmonary changes. There was obliterative endarteritis of the left coronary branch and pulmonary arteries. The interstitial pulmonary fibrosis was also prominent. The pancytopenia should have been induced by the mechanical damage of circulating blood cells by the left atrial myxoma. The pathological findings of the lungs were highly suggestive of pulmonary hypertension, which was assumed to be due to mitral block caused by the atrial myxoma.

Benign primary cardiac tumors are rare and about half of these is myxoma. They usually occur in the atria and are approximately 75 per cent in the left atrium. Diagnosis of cardiac myxomas is often difficult because of confused array of signs and symptoms, which may simulate mitral stenosis or subacute bacterial endocarditis. GooDWIN (1) divided clinical manifestations of cardiac tumors into four groups; hemodynamic disturbances, mechanical hemolysis, biochemical effects and constitutional symptoms.

In the case presented here, of special interest is that attacks of hemolytic anemia, thrombocytopenia and leukocytopenia occurred in a patient with the clinical picture of far advanced congestive heart failure, accompanied by remittent fever and jaundice. Postmortem examination revealed a left atrial myxoma and the changes that suggested pulmonary hypertension.

433

1 Kawanishi et al.: A case of left atrial myxoma accompanied by pancytopenia and

Produced by The Berkeley Electronic Press, 1974

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434 K. KAWANlSHI, K. SATO, T. OFUJI and K. OGAWA

CASE REPORT

The patient was a l5-year old school boy and h'td always felt well until March 1969, when he was first noticed of systolic murmur at the apex of his heart on the physical examination. In the morning of August 8, 1969, he developed a sudden onset of abdominal pain and coldness of his right lower leg and foot. He was admitted to the Surgical Department of Okayama University Hospital for an anticoagulant therapy for the embolism of the right femoral artery and further evaluation of the cardiac condition. During the hospitalization, he had a persistent low grade of fever. As a result of a cardiac catheterization, he was diagnosed as possible mitral stenosis with subacute bacterial endocarditis. The patient was discharged from the surgical ward in September 1969. But his cardiac condition gradually worsened, with developing generalized malaise, palpitation, dyspnea and swelling of the liver. He was readmitted to the surgical ward of the Univer- sity Hospital on January 8, 1970. Physical examination showed a remark- ably dilated heart with grade II diastolic rumbling murmur at the apex· of the heart and the markedly enlarged liver. Erythrocyte sedimentation rate was 5 mm/h, ASLO 12 units, CRP 3

+ .

Hematological data revealed red blood cells (RBC) 464 x 104/cmm, hemoglobin (Hb) 9.4 gldl, white blood cells (WBC) l2,500/cmm, hematocrit (Ht) 31%. Total bilirubin was 1.57 mg/dl, direct bilirubin 0.67 mg/dl, SCOT 21 units and SCPT 77 units.

In the beginning of February, the patient had the right pleural effusion and moderate pitting edema on his legs. This congestive heart failure responded poorly to digitalis and diuretics. And he became more anemic and icteric.

He was transferred to the medical ward on March 18, 1970 for a further medical treatment. Physical examination on admission revealed a thin, pale and icteric boy with signs of far advanced congestive heart failure. The radial pulse was rapid but regular. Arterial blood pressure was 102/52 mmHg. The jugular veins were distended. The heart was markedly dilated bilaterally; 5 cm to the right and 8 cm to the left, with a grade III systolic murmur at the apex. There was dullness in the right chest. The liver extended by about 17 cm below the right costal margin. The spleen was not papable. He had ankle edema. His temperature was 36. 7°C.

Laborator)1Findings: The erythrocyte sedimentation rate showed 1mmlh and 4 mm/2h. The hematological data on admission and during the sub- sequent hospitalization (Table 1 and Fig. 1) indicated that the patient had attacks of severe anemia with reticulocytosis, thrombocytopenia and leukocytopenia with relative neutrophilia at the same time. Study of sternal bone marrow showed a marked erythroid hyperplasia and a normal amount of

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Left Atrial Myxoma 435 megakartocytes. Total serum bilirubin was 4. 12 mg/dl and indirect bilirubin 1. 66 mg/dl (Table 1 and Fig. 1). The SGOT was 37 units, and SGPT

TABLE 1 HEMATOLOGICAL DATA AND SERUM BILIRUBIN LEVELS DURING THE HOSPITALIZATION.

3-18-70 4-30-70 5-18-70 6-9-70 8-24-70 9-5-70 (on admission) (1st attack) (2nd attack) (3rd attack)

RBC (x10) 370 144 365 149 302 190

Hb (%) 20 28 37

Ht (%) 18 28 21

Reticulocyte(%0) 27 7 6 1

Platelet (x104 ) 5.35 4.8 8. 76 2.38 20.0 0.57

WBC 10200 5040 9600 3600 6800 1100

Neutrophil (%) 51 69 67 87 86

Lymphocyte (%) 45 31 27 3 12

Total 4.12 5.68 6.07 6.31 1. 78 1. 71

bilirubin (mg/dl) Indirect

1.66 2.30 2.40 2.85 0.71 0.47

bilirubin (mg/dl)

32 units. The colloidal reactions were within normal limits. The serum iron level was 23,ug/dl, serum Na 120 mEg/I, K 5.0 mEg/I. The total serum protein was 5.0 g/dl with 70 per cent of albumin, 4 per cent al-, 6 per cent

az-,

8.5 per cent (3-, 11. 5 per cent r-globulin, AIG ratio 2. 33.

ASLO was 100 units (Todd), RA test and antinuclear factor negative, serum complement titer (CH50) 22.5. The chest roentgenogram (Fig. 2) showed a marked cardiomegaly, with pulmonary congestion and right pleural effusion.

The electrocardiogram revealed sinus tachycardia and non-specific ST-T changes, that showed depressed ST and diphasic or inverted T waves. '"

Hospital Course: The patient was put on digitalization and diuretic therapy, which responded poorly on him. In the end of March 1970, he developed low grade of fever. On April 30, 1970, he looked very tired and his lips were markedly pale. His skin became more icteric. The hematological data showed acute attack of hemolysis. The smear of the blood cells showed helmet-shaped erythrocytes. Direct and indirect Coombs' tests were negative. The osmotic fragility test of erythrocyte ranged fromO.42 to 0.30 per cent. After he was transfused 1,200 ml of fresh whole blood, his general condition improved in spite of temperature elevation. In the beginning of June, he experienced the second attack of the severe anemia accompanied by the thrombocytopenia and moderate leukocytopenia. The bleeding time was prolonged more than 10 minutes. The occult blood of stool was positive.

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436

K. KAWANISHI, K, SATO, T. OFUJI and K. OGAWA

1970

Morch Apr i I Moy June JuIy AUQust Sept.

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Fig. 1. Hospital course.

Numerous petechiae were seen on the skin and mucous membrane. He was given 800 ml of whole blood and 200 ml of thrombocyte suspension blood.

Also he was administered 10 mg of prednisolone daily and 0.25 to 0.5 mg ACTH twice a week for 8 weeks. With the steroid administration, his urinary output increased up to 3,000 ml per day and the right pleural effusion was disappeared. The ascites and pitting edema of the extremities were decreased. The size of the liver became smaller. The cardiac silhouette on

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Left Atrial Myxoma 437 x-ray film was reduced in size. But his temperature remained remittent, showing the highest of 40°C. Several laboratory studies were carried out;

arterial blood culture showed no organism, Widal, Weil-Fe1ix and Paul- Bunnell test were negative. Repeated Coombs' tests were entirely negative.

Fig. 2. Chest X-rayon admission to the medical ward. There were prominent enlar- gement of cardiac silhouette and right pleural effusion.

Fig. 3. Autopsy finding of the heart. Upper arrow indicates a left atrial myxoma, which was attached to the posterior wall of the atrium with a pedicle. Lower arrow indicates multiple infarct scars of the anterior wall.

Immunoglobulins of the blood were IgG 700 mg/dl, IgA 107 mg/dl, IgM 22 mg/dt The chest roentgenogram on August 8, 1970, showed diffuse small miliary nodular infiltrations throughout both lungs. Culture of the sputum revealed Neisseria, Klebsiella and Candida, but no tubercle bacillus.

The erythrocyte sedimentation rate was 62 mm/h, CRP 6

+.

The remittent f ever responded poorly to steroid and antibiotics administration. However, in the end of August, the temperature fell to normal ranges spontaneously.

The chest x-ray showed no definite infiltrations any more. Electrocardiograms revealed tall and peaked P waves, without any remarkable ST-T changes.

In the beginning of September, the patient suffered the third attack of the anemia, marked thrombocytopenia and leukocytopenia accompanied by hemorrhagic tendency at the same time. He was given 200 ml of whole blood transfusion, but his general condition rapidly deteriorated and on September 15, 1970, he died of the right pneumothorax.

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438 K. KAWANISHI, ':K. SATO, T. OFUJI and K. OGAWA

:Hain Autops), Findings:

Heart (Fig. 3) : Weigh"ed 340 g. In the left atrium, a pedunculated gelatinous tumor in the size of 6x4x3. 5 cm was found. It was attached to the posterior wall of the atrium with a pedicle laying its apex within the mitral value cusps. Grossly and microscopically, the tumor was a myxoma. The left atrium and ventricle were dilated and the left ventricle was hypertrophied.

There were obliterative endarteritis of the descending branch of the left coronary artery (Fig. 4) and mul tiple infarct scars of the anterior wall.

Fig. 4. Transverse section of the descending branch of the left coronary artery. The vessel is markedly narrowed, both by prominent intimal proliferation and organization.

X100.

Fig. 5. Transverse section of a small pulmonary artery in the areas of interstitial fibrosis. There are medial hypertrophy and intimal proliferation accompanied by throm- bus formation. X400.

Lungs: There were left fibrinoid pleuritis and right spontaneous pneumothorax.

Microscopic observation showed interstitial fibrosis, hemorrhagic infarctions and pneumonia with partially organized fibrinous exudation of the bilateral lungs. Cytomegalic inclusion bodies were seen in the right middle lobe. In the areas of interstitial fibrosis the small and medium sized pulmonary arteries were often markedly narrowed. Histologically, this was obliterative thrombotic endarteritis (Fig. 5).

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Left Atrial Myxoma

439

The liver weighed 1560 g. There were fatty infiltration, bleeding and fibrinoid necrosis of the central areas.

DISCUSSION

The case presented above was a typical case of the left atrial myxoma, and satisfied almost all of the symptoms of diagnostic criteria for cardiac tumors described by GOODWIN (1). However, the most interesting features of this case were the associated attacks of severe pancytopenic syndrome and obliterative endarteritis of the cardiopulmonary system.

Anemia is often mentioned among the systemic manifestations of atrial myxoma. But the anemia accompanying left atrial myxoma is occasionally caused also by mechanical hemolysis (1). It is said about this symptom that very similar pathologic abnormalities of red blood cells are seen in patients with heavily calcified aortic valves (2) and prosthetic valves (3). The red cells are destroyed in excessive numbers by the damaging effect of the moving tumor. VUOPIOand NIKKILA (4) reported a case of left atrial myxoma associated with mitral stenosis which developed profuse hemolytic anemia with increased level of serum indirect bilirubin and thrombocytopenia giving rise to petechial bleedings. Morphologic observation indicated this hemolytic anemia was induced by the intense erythropoiesis. They suggested that both red blood cells and platelets were destroyed or injured in the intracardiac blood whirls.

An additional interesting feature of this case was leukocytopenia, which might have been produced also by mechanical leukocytolysis. Thre~ attacks of the pancytopenia seemed to occur when the red cell counts exceeded

300X104/cmm.

In cases of left atrial myxoma, general constitutional disturbances may be seen (1, 5, 6, 7). These are cachexia, fever, anorexia, malaise, high erythrocyte sedimentation rate, abnormal serum proteins, anemia and positive C-reactive protein. The symptoms may mimic the collagen diseases. The etiology of the general constitutional symptoms is unknown, but there have been described some immunological speculations, which include systemic reaction due to hemorrhage or necrosis of the tumor (5), immune response to fragments of tumor released into circulation (8), and autoimmune state analo- gous to that seen after cardiotomy or myocardial infarction (9). The case of atrial myxoma described by CATT and his associates (10) responded to steroid.

Administration of steroid in our case increased urinary output followed by im- provement of congestive heart failure.

Autopsy findings in our case of the obliterative endarteritis of the pulmonary arteries and the hemorrhagic infarctions with intricate pulmonary

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440 K. KAWANISHI, K. SATO, T. OFUJI and K. OGAWA

changes might have been caused by pulmonary hypertension, which was assumed to be due to mitral block caused by atrial myxoma. In the left atrial tumor, the pulmonary hypertension develops by the same mechanism as in mitral stenosis (11). Here the pulmonary vascular changes are very similar to those found in mitral stenosis, with medial hypertrophy of muscular pulmonary arteries and exudative changes with pulmonary congestions and hemo- siderosis with interstitial fibrosis. The cases of left atrial myxoma reported by SOLOMON (12) and HARVEY (6) showed interstitial pulmonary fibrosis secondary to pulmonary venous hypertension. ANDREWS' case (13) showed interstitial pulmonary fibrosis and obliterative endarteritis of the lung. It is considered that these changes can be placed in the category of pulmo cardialis (14). It is assumed that the obliterative endarteritis of the left coronary branch in our case might cause multiple infarctions of the anterior wall of the left ventricle. The possibility of thrombotic thrombocytopenic purpura was excluded by the absence of platelet thrombosis at autopsy. In addition to these changes, bacterial or viral infections per se and additional allergic in- flammations caused by the infections seemed to have caused complicated pulmonary changes.

REFERENCES

I. GOODWIN, J.F.: The spectrum of cardiac tumors. Am. J. Cardiol. 21, 307-314, 1968 2. Case records of the Massachusetts General Hospital (Case 52-1964). New Eng. J. Med.

271, 898-905, 1964

3. WALSH,J.R., STARR, A. and RITZMANN, L. W.: Intravascular hemolysis in patients with prosthetic valves and vascular heart disease. SupplementI toCirculationVols 39 and 40, I:

135-140, 1969

4. VUOPIO, P. and NIKKILA, E. A.: Hemolytic anemia and thrombocytopenia in a case of left atrial myxoma associated with mitral stenosis. Am.J. Cardiol. 17, 585-589, 1966 5. LEKISCH, K.: Myxoma of the left atrium: Report of a case. Ann. Intern. Med. 46, 982-

990, 1957

6. HARVEY,J.C.: Myxoma of the left auricle. Ann. Intern. Med. 47, 1067-1081, 1957 7. MACGREGOR, G. A. and CULLEN, R. A.: The syndrome of fever, anemia, and high sedi-

mentation rate with an atrial myxoma. Brit. Med. J. 14, 991-993, 1959

8. Boss, J.H. and BECHER, M.: Myxoma of the heart: Report based on four cases. Am. J.

Cardiol. 3, 823-828, 1959

9. CURREY, H.L. F. and MATHEWS, j. A.: Right atrial myxoma mimicking a rheumatic dis- order. Brit. Med. J. 1, 547-548, 1967

10. CATT, K., DENBOROUGH, M. A., LINDSAY GRIGG and GRAEME SLOMAN: Myxoma of the right atrium. Brit. HeartJ. 24, 525-528, 1962

11. HEATH, D.: Pathology of cardiac tumots. Am. J. Cardiol. 21, 315-327, 1968

12. SOLOMON, M.: Interstitial pulmonary fibrosis secondary to pulmonary venous hypertension. Report of a case due to myxoma of the left atrium.J.A. M. A. 174,464-467, 1960 13. ANDREWS, E. C. jr.: Five cases of an undescribed form of pulmonary veins. Bull. John

Hopkins Hosp. 100, 28-42, 1957

14. SAKAMOTO, H. and KUNIEDA, T.: Contributions to the concept of" pu1mo cardia1is."J.

Clinical Science8, 151-159, 1972 (in japanese)

A case of left atrial myxoma accompanied by pancytopenia and pathological findings

Acta Medica Okayama

D

1974

A case of left atrial myxoma accompanied by pancytopenia and pathological findings

suggestive of pulmonary hypertension

suggestive of pulmonary hypertension ∗

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